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1. 发明授权

US08853167B2 Short-chain cationic polyamino acid and use thereof 有权
标题翻译：短链阳离子聚氨基酸及其用途
公开(公告)号：US08853167B2
公开(公告)日：2014-10-07
申请号：US13258663
申请日：2011-02-23
申请人： Yasuki Kato , Atsushi Ishii , Naoya Shibata , Tatsuyuki Hayashi , Kazunori Kataoka , Kanjiro Miyata , Nobuhiro Nishiyama
发明人： Yasuki Kato , Atsushi Ishii , Naoya Shibata , Tatsuyuki Hayashi , Kazunori Kataoka , Kanjiro Miyata , Nobuhiro Nishiyama
IPC分类号： A61K47/48 , C08G69/10 , C12N15/11
CPC分类号： C08G69/10 , A61K47/60 , A61K47/6455 , C12N15/111 , C12N2310/14 , C12N2320/32
摘要： The present invention provides a cationic polyamino acid suitable for a carrier that can form a stable complex with a nucleic acid under a physiological condition and release the nucleic acid in cells suitably. The cationic polyamino acid can associate with a nucleic acid and includes a cationic amino acid residue having a cationic group in a side chain and a hydrophobic amino acid residue having a hydrophobic group in a side chain. The cationic polyamino acid includes 1 to 20 units of the cationic amino acid residue and is represented by the following formula (1). The meaning of each symbol in the formula is as shown in the description.
摘要翻译：本发明提供一种适用于可在生理条件下与核酸形成稳定复合物的载体的阳离子聚氨基酸，并适当地释放细胞中的核酸。阳离子聚氨基酸可以与核酸结合，并且包括在侧链中具有阳离子基团的阳离子氨基酸残基和在侧链中具有疏水基团的疏水性氨基酸残基。阳离子聚氨基酸包含1〜20个单元的阳离子氨基酸残基，由下式（1）表示。公式中每个符号的含义如说明书所示。

2. 发明申请

US20120149649A1 SHORT-CHAIN CATIONIC POLYAMINO ACID AND USE THEREOF 有权
标题翻译：短链阳离子聚氨酯酸及其用途
公开(公告)号：US20120149649A1
公开(公告)日：2012-06-14
申请号：US13258663
申请日：2011-02-23
申请人： Yasuki Kato , Atsushi Ishii , Naoya Shibata , Tatsuyuki Hayashi , Kazunori Kataoka , Kanjiro Miyata , Nobuhiro Nishiyama
发明人： Yasuki Kato , Atsushi Ishii , Naoya Shibata , Tatsuyuki Hayashi , Kazunori Kataoka , Kanjiro Miyata , Nobuhiro Nishiyama
IPC分类号： A61K38/16 , C07K7/08 , A61P43/00 , A61K38/08 , A61K38/10 , C07K7/06 , C07K14/00
CPC分类号： C08G69/10 , A61K47/60 , A61K47/6455 , C12N15/111 , C12N2310/14 , C12N2320/32
摘要： The present invention provides a cationic polyamino acid suitable for a carrier that can form a stable complex with a nucleic acid under a physiological condition and release the nucleic acid in cells suitably. The cationic polyamino acid can associate with a nucleic acid and includes a cationic amino acid residue having a cationic group in a side chain and a hydrophobic amino acid residue having a hydrophobic group in a side chain. The cationic polyamino acid includes 1 to 20 units of the cationic amino acid residue and is represented by the following formula (1). The meaning of each symbol in the formula is as shown in the description.
摘要翻译：本发明提供一种适用于可在生理条件下与核酸形成稳定复合物的载体的阳离子聚氨基酸，并适当地释放细胞中的核酸。阳离子聚氨基酸可以与核酸结合，并且包括在侧链中具有阳离子基团的阳离子氨基酸残基和在侧链中具有疏水基团的疏水性氨基酸残基。阳离子聚氨基酸包含1〜20个单元的阳离子氨基酸残基，由下式（1）表示。公式中每个符号的含义如说明书所示。

3. 发明申请

US20110052917A1 COPOLYMER INCLUDING UNCHARGED HYDROPHILIC BLOCK AND CATIONIC POLYAMINO ACID BLOCK HAVING HYDROPHOBIC GROUP IN PART OF SIDE CHAINS, AND USE THEREOF 有权
标题翻译：共聚物包括在侧链部分的疏水性嵌段和阳离子聚氨酯嵌段，并使用它们
公开(公告)号：US20110052917A1
公开(公告)日：2011-03-03
申请号：US12922116
申请日：2009-03-06
申请人： Kazunori Kataoka , Nobuhiro Nishiyama , Atsushi Ishii , Yasuki Kato , Kanjiro Miyata , Hyunjin Kim , Hiroyasu Takemoto
发明人： Kazunori Kataoka , Nobuhiro Nishiyama , Atsushi Ishii , Yasuki Kato , Kanjiro Miyata , Hyunjin Kim , Hiroyasu Takemoto
IPC分类号： B32B27/00 , C08G69/48 , B82Y5/00
CPC分类号： C08G69/10 , C08G81/00 , Y10T428/2982
摘要： The present invention relates to a block copolymer containing an uncharged hydrophilic polymer chain block and a cationic polyamino acid chain block, wherein the hydrophilic polymer chain block is covalently bound to one end of the main chain of the polyamino acid chain block, and the hydrophobic group is covalently bound to the side chains of not less than 10% and not greater than 70% of amino acid repeating units in the polyamino acid chain block. This block copolymer forms a stable aggregate with siRNA, a small-molecule nucleic acid, under a physiological condition.
摘要翻译：本发明涉及含有不带电荷的亲水性聚合物链段和阳离子聚氨基酸链嵌段的嵌段共聚物，其中亲水性聚合物链嵌段共价键合到聚氨基酸链嵌段的主链的一端，疏水基与聚氨基酸链嵌段中氨基酸重复单元的侧链共价结合不少于10％且不大于70％。该嵌段共聚物在生理条件下与siRNA（小分子核酸）形成稳定的聚集体。

4. 发明授权

US08431545B2 Copolymer including uncharged hydrophilic block and cationic polyamino acid block having hydrophobic group in part of side chains, and use thereof 有权
标题翻译：包括不带电荷的亲水嵌段和在一部分侧链具有疏水基团的阳离子聚氨基酸嵌段的共聚物及其用途
公开(公告)号：US08431545B2
公开(公告)日：2013-04-30
申请号：US12922116
申请日：2009-03-06
申请人： Kazunori Kataoka , Nobuhiro Nishiyama , Atsushi Ishii , Yasuki Kato , Kanjiro Miyata , Hyunjin Kim , Hiroyasu Takemoto
发明人： Kazunori Kataoka , Nobuhiro Nishiyama , Atsushi Ishii , Yasuki Kato , Kanjiro Miyata , Hyunjin Kim , Hiroyasu Takemoto
IPC分类号： A61K48/00 , A61K38/00 , A61K47/00 , A61K9/127 , A61K9/14 , A61P35/00 , A01N25/00
CPC分类号： C08G69/10 , C08G81/00 , Y10T428/2982
摘要： The present invention relates to a block copolymer containing an uncharged hydrophilic polymer chain block and a cationic polyamino acid chain block, wherein the hydrophilic polymer chain block is covalently bound to one end of the main chain of the polyamino acid chain block, and the hydrophobic group is covalently bound to the side chains of not less than 10% and not greater than 70% of amino acid repeating units in the polyamino acid chain block. This block copolymer forms a stable aggregate with siRNA, a small-molecule nucleic acid, under a physiological condition.
摘要翻译：本发明涉及含有不带电荷的亲水性聚合物链段和阳离子聚氨基酸链嵌段的嵌段共聚物，其中亲水性聚合物链嵌段共价键合到聚氨基酸链嵌段的主链的一端，疏水基与聚氨基酸链嵌段中氨基酸重复单元的侧链共价结合不少于10％且不大于70％。该嵌段共聚物在生理条件下与siRNA（小分子核酸）形成稳定的聚集体。

5. 发明申请

US20120196810A1 ANIONIC POLYMER, POLYION COMPLEX AND TERNARY POLYMER COMPOSITE USING ANIONIC POLYMER, AND PHARMACEUTICAL COMPOSITION 有权
标题翻译：使用阴离子聚合物和药物组合物的阴离子聚合物，聚合物和季铵盐聚合物复合物
公开(公告)号：US20120196810A1
公开(公告)日：2012-08-02
申请号：US13386554
申请日：2010-07-23
申请人： Kazunori Kataoka , Atsushi Ishii , Hiroyasu Takemoto , Masataka Nakanishi , Nobuhiro Nishiyama , Kanjiro Miyata
发明人： Kazunori Kataoka , Atsushi Ishii , Hiroyasu Takemoto , Masataka Nakanishi , Nobuhiro Nishiyama , Kanjiro Miyata
IPC分类号： A61K38/14 , C07K2/00
CPC分类号： C08L79/02 , C08G69/10 , C08G73/0206 , C08G73/028 , C08L77/04
摘要： There are provided an anionic polymer, a polyion complex, and a ternary polymer composite, each of which is stable in a biological environment and is capable of realizing small RNA delivery without causing any undesired immune response. An anionic polymer according to an embodiment of the invention includes: a main chain which includes repeating units having carboxyl groups; and a side chain which is linked with part of the carboxyl groups in the main chain and is represented by the following formula: -A-B—X where : A represents a residue having one or more aminoethyl bonds; B represents an in vivo cleavable bond; and X represents a small RNA. A polyion complex according to an embodiment of the invention includes the anionic polymer as described above and a cationic polymer. A ternary polymer composite according to an embodiment of the invention includes the polyion complex as described above and a charge conversional polymer.
摘要翻译：提供阴离子聚合物，聚离子络合物和三元聚合物复合材料，其中每一种在生物环境中都是稳定的并且能够实现小的RNA递送而不引起任何不期望的免疫应答。根据本发明实施方案的阴离子聚合物包括：主链，其包含具有羧基的重复单元; 和与主链中部分羧基连接并由下式表示的侧链：-A-B-X其中：A表示具有一个或多个氨基乙基的残基; B代表体内可剪切键; X表示小RNA。根据本发明实施方案的聚离子络合物包括如上所述的阴离子聚合物和阳离子聚合物。根据本发明实施方案的三元聚合物复合物包括如上所述的聚离子络合物和电荷转移聚合物。

6. 发明授权

US08450282B2 Anionic polymer, polyion complex and ternary polymer composite using anionic polymer, and pharmaceutical composition 有权
标题翻译：阴离子聚合物，聚离子络合物和三元聚合物复合材料使用阴离子聚合物，以及药物组成
公开(公告)号：US08450282B2
公开(公告)日：2013-05-28
申请号：US13386554
申请日：2010-07-23
申请人： Kazunori Kataoka , Atsushi Ishii , Hiroyasu Takemoto , Masataka Nakanishi , Nobuhiro Nishiyama , Kanjiro Miyata
发明人： Kazunori Kataoka , Atsushi Ishii , Hiroyasu Takemoto , Masataka Nakanishi , Nobuhiro Nishiyama , Kanjiro Miyata
IPC分类号： A61K38/00 , C07K14/72 , C07K14/705
CPC分类号： C08L79/02 , C08G69/10 , C08G73/0206 , C08G73/028 , C08L77/04
摘要： There are provided an anionic polymer, a polyion complex, and a ternary polymer composite, each of which is stable in a biological environment and is capable of realizing small RNA delivery without causing any undesired immune response. An anionic polymer according to an embodiment of the invention includes: a main chain which includes repeating units having carboxyl groups; and a side chain which is linked with part of the carboxyl groups in the main chain and is represented by the following formula: -A-B—X where: A represents a residue having one or more aminoethyl bonds; B represents an in vivo cleavable bond; and X represents a small RNA. A polyion complex according to an embodiment of the invention includes the anionic polymer as described above and a cationic polymer. A ternary polymer composite according to an embodiment of the invention includes the polyion complex as described above and a charge conversional polymer.
摘要翻译：提供阴离子聚合物，聚离子络合物和三元聚合物复合材料，其中每一种在生物环境中都是稳定的并且能够实现小的RNA递送而不引起任何不期望的免疫应答。根据本发明实施方案的阴离子聚合物包括：主链，其包含具有羧基的重复单元; 和与主链中部分羧基连接并由下式表示的侧链：-A-B-X其中：A表示具有一个或多个氨基乙基的残基; B代表体内可剪切键; X表示小RNA。根据本发明实施方案的聚离子络合物包括如上所述的阴离子聚合物和阳离子聚合物。根据本发明实施方案的三元聚合物复合物包括如上所述的聚离子络合物和电荷转移聚合物。

7. 发明授权

US09198860B2 Particulate pharmaceutical composition 有权
标题翻译：颗粒状药物组成
公开(公告)号：US09198860B2
公开(公告)日：2015-12-01
申请号：US13122546
申请日：2011-02-14
申请人： Atsushi Ishii , Yasuki Kato
发明人： Atsushi Ishii , Yasuki Kato
IPC分类号： A61K9/14 , A61K31/7088 , A61K38/02 , A61K9/107 , A61K31/7084 , A61K9/16 , A61K9/19 , A61K47/24 , A61K47/34
CPC分类号： A61K9/1075 , A61K9/16 , A61K9/19 , A61K31/7084 , A61K31/713 , A61K47/24 , A61K47/34
摘要： The present invention provides a particulate pharmaceutical composition which has improved drug encapsulation stability and is suitable for a drug delivery system. The particulate pharmaceutical composition 1 contains: a plurality of block copolymer unit 2 arranged radially, each of which has a hydrophobic polymer-chain segment 2b, which is arranged radially inside, and a hydrophilic polymer-chain segment 2a, which is arranged radially outside; a drug 4, which includes a biomacromolecule; and a charged lipid 3, which has an electrical charge opposite to that of the drug 4; wherein the charged lipid 3 is being attracted to the hydrophobic polymer-chain segment 2b, and the drug 3 is positioned radially inside the hydrophobic polymer-chain segment 2b. The pharmaceutical composition 1 can effectively prevent the drug 4 from disengaging from the particle.
摘要翻译：本发明提供了具有改善的药物包封稳定性并且适合于药物递送系统的颗粒药物组合物。颗粒状药物组合物1包含：径向配置的多个嵌段共聚物单元2，其各自具有径向配置的疏水性聚合物链段2b和位于径向外侧的亲水性聚合物链段2a; 包括生物大分子的药物4; 和带电荷的脂质3，其具有与药物4的电荷相反的电荷; 其中带电脂质3被吸引到疏水聚合物链段2b，并且药物3位于疏水性聚合物链段2b的径向内侧。药物组合物1可以有效地防止药物4与粒子分离。

8. 发明授权

US09415059B2 Particulate composition and pharmaceutical composition containing the same 有权
标题翻译：颗粒组成和含有它的药物组合物
公开(公告)号：US09415059B2
公开(公告)日：2016-08-16
申请号：US13381841
申请日：2010-08-31
申请人： Yasuki Kato , Atsushi Ishii
发明人： Yasuki Kato , Atsushi Ishii
IPC分类号： A61K38/16 , A61K31/7088 , A61K9/107 , A61K9/127 , A61K31/715 , A61K38/38 , C12N15/88
CPC分类号： A61K31/7088 , A61K9/107 , A61K9/1271 , A61K9/1272 , A61K31/715 , A61K38/38 , C12N15/88
摘要： The present invention provides a particulate composition containing: block copolymer units being arranged radially with hydrophobic polymer-chain segments radially inside and hydrophilic polymer-chain segments radially outside; and a charged lipid which carries a charge opposite to the charge of a drug to be encapsulated, the charged lipid being attracted to the hydrophobic polymer-chain segment. In this particulate composition, the drug is retained within the particle via electrostatic binding with the charged lipid, whereby the outer surface of the particle is prevented from being charged to attract a substance which has a charge opposite to that of the charged lipid.
摘要翻译：本发明提供了一种颗粒组合物，其含有：径向排列有疏水性聚合物链段的径向外侧和亲水性聚合物链段径向外侧的嵌段共聚物单元; 和带电脂质，其带有与要包封的药物的电荷相反的电荷，带电脂质被吸引到疏水性聚合物链段。在该颗粒组合物中，药物通过与带电脂质的静电结合而保留在颗粒内，从而防止颗粒的外表面被带电以吸引具有与带电脂质相反的电荷的物质。

9. 发明申请

US20120107377A1 PARTICULATE COMPOSITION AND PHARMACEUTICAL COMPOSITION CONTAINING THE SAME 有权
标题翻译：颗粒组合物和含有该组合物的药物组合物
公开(公告)号：US20120107377A1
公开(公告)日：2012-05-03
申请号：US13381841
申请日：2010-08-31
申请人： Yasuki Kato , Atsushi Ishii
发明人： Yasuki Kato , Atsushi Ishii
IPC分类号： A61K47/34 , A61K38/02 , A61K31/7088 , A61K9/18
CPC分类号： A61K31/7088 , A61K9/107 , A61K9/1271 , A61K9/1272 , A61K31/715 , A61K38/38 , C12N15/88
摘要： The present invention provides a particulate composition containing: block copolymer units being arranged radially with hydrophobic polymer-chain segments radially inside and hydrophilic polymer-chain segments radially outside; and a charged lipid which carries a charge opposite to the charge of a drug to be encapsulated, the charged lipid being attracted to the hydrophobic polymer-chain segment. In this particulate composition, the drug is retained within the particle via electrostatic binding with the charged lipid, whereby the outer surface of the particle is prevented from being charged to attract a substance which has a charge opposite to that of the charged lipid.
摘要翻译：本发明提供了一种颗粒组合物，其含有：径向排列有疏水性聚合物链段的径向外侧和亲水性聚合物链段径向外侧的嵌段共聚物单元; 和带电脂质，其带有与要包封的药物的电荷相反的电荷，带电脂质被吸引到疏水性聚合物链段。在该颗粒组合物中，药物通过与带电脂质的静电结合而保留在颗粒内，从而防止颗粒的外表面被带电以吸引具有与带电脂质相反的电荷的物质。

10. 发明申请

US20120076866A1 PARTICULATE PHARMACEUTICAL COMPOSITION 有权
标题翻译：颗粒状药物组合物
公开(公告)号：US20120076866A1
公开(公告)日：2012-03-29
申请号：US13122546
申请日：2011-02-14
申请人： Atsushi Ishii , Yasuki Kato
发明人： Atsushi Ishii , Yasuki Kato
IPC分类号： A61K9/14 , A61K31/7088 , A61K38/02
CPC分类号： A61K9/1075 , A61K9/16 , A61K9/19 , A61K31/7084 , A61K31/713 , A61K47/24 , A61K47/34
摘要： The present invention provides a particulate pharmaceutical composition which has improved drug encapsulation stability and is suitable for a drug delivery system. The particulate pharmaceutical composition 1 contains: a plurality of block copolymer unit 2 arranged radially, each of which has a hydrophobic polymer-chain segment 2b, which is arranged radially inside, and a hydrophilic polymer-chain segment 2a, which is arranged radially outside; a drug 4, which includes a biomacromolecule; and a charged lipid 3, which has an electrical charge opposite to that of the drug 4; wherein the charged lipid 3 is being attracted to the hydrophobic polymer-chain segment 2b, and the drug 3 is positioned radially inside the hydrophobic polymer-chain segment 2b. The pharmaceutical composition 1 can effectively prevent the drug 4 from disengaging from the particle.
摘要翻译：本发明提供了具有改善的药物包封稳定性并且适合于药物递送系统的颗粒药物组合物。颗粒状药物组合物1包含：径向配置的多个嵌段共聚物单元2，其各自具有径向配置的疏水性聚合物链段2b和位于径向外侧的亲水性聚合物链段2a; 包括生物大分子的药物4; 和带电荷的脂质3，其具有与药物4的电荷相反的电荷; 其中带电脂质3被吸引到疏水聚合物链段2b，并且药物3位于疏水性聚合物链段2b的径向内侧。药物组合物1可以有效地防止药物4与粒子分离。

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